Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma
Primary Purpose
Hodgkin Lymphoma, Classic Hodgkin Lymphoma, Relapsed Classical Hodgkin Lymphoma
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Magrolimab
Pembrolizumab
PET/CT
Sponsored by
About this trial
This is an interventional treatment trial for Hodgkin Lymphoma
Eligibility Criteria
Inclusion Criteria:
- Age ≥ 18 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
- Biopsy proven relapsed or refractory cHL
- Prior treatment with at least two systemic therapies
- Metabolically active measurable disease by PET imaging per the 2014 Lugano criteria
- Hemoglobin ≥ 9.5 g/dL
- Absolute neutrophil count ≥ 1,000 cells/μL without G-CSF support within 3 weeks prior to enrollment
- Platelet count ≥ 75,000 cells/μL
- Creatinine clearance > 40 mL/min per the Cockroft-Gault formula
- Total bilirubin < 1.5 x upper limit of normal (ULN) (or < 3.0 x ULN and primarily unconjugated in subjects with a history of Gilbert's syndrome)
- Negative urine or serum pregnancy test within 30 days of enrollment and within 72 hours before the first administration of magrolimab for women of childbearing potential
- Women of childbearing potential must be willing to use at least 1 highly effective method of contraception during the study and continue for 4 months after the last dose of magrolimab
- Male subjects who are sexually active with a woman of childbearing potential and who have not had vasectomies must be willing to use a barrier method of contraception during the study and for 4 months after the last dose of magrolimab
- Ability to understand and the willingness to sign the written IRB approved informed consent document
- Must be willing and able to comply with the clinic visits and procedures outlined in the study protocol
Exclusion Criteria:
- Prior treatment with a PD-1 inhibitor within 6 months prior to enrollment
- Prior treatment with antibodies targeting CD47 or SIRPα2
- Prior allogeneic hematopoietic cell transplantation
- Systemic autoimmune disorder on chronic immunosuppression (defined as ≥ 10 mg of prednisone daily)
- RBC transfusion dependence, defined as requiring more than 2 units of RBCs during the 4-week period prior to screening
- History of hemolytic anemia, autoimmune thrombocytopenia, or Evan's syndrome within the last 3 months
- Second malignancy not in complete remission for at least 1 year, excluding fully resected non melanoma skin cancer or localized prostate cancer
- Women who are pregnant or breast feeding
- HIV or hepatitis B or C infection with active viral replication by PCR
- Second malignancy not in complete remission for at least 1 year, excluding fully resected non-melanoma skin cancer or localized prostate cancer
- Active cardiac disease including unstable angina, decompensated congestive heart failure, or severe uncontrolled conduction abnormalities
- History of non-infectious pneumonitis requiring corticosteroids or current pneumonitis
- Significant medical conditions, as assessed by the investigators and IND holder, that would substantially increase the risk benefit ratio of participating in the study
- History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements
- Received a live or live attenuated vaccine within 30 days before the first dose of study intervention
- Received any anti-cancer therapy within 2 weeks prior to the first dose of study intervention
Sites / Locations
- Stanford UniversityRecruiting
- Dana Farber Cancer InstituteRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Magrolimab (Hu5F9 G4) and pembrolizumab
Arm Description
All subjects will have a baseline PET CT and excisional or core needle biopsy within 1 month of study enrollment and baseline electrocardiogram and laboratory studies within 1 week of study enrollment. All subjects will receive treatment with magrolimab and pembrolizumab according to the dosing schedule. Magrolimab IV given on cycle 1, 2 and 3. Pembrolizumab 200 mg IV given on Cycle 1, 2 and 3. Patients may continue to receive treatment on the study for a maximum of 24 months or until progression of disease, unacceptable toxicity, or bridge to stem cell transplantation (SCT).
Outcomes
Primary Outcome Measures
Complete Response (CR)
Each participant's response to treatment will be assessed per the Lugano criteria. The criteria are:
Complete Response (CR): Complete disappearance of all lesions, evidence, and effects of disease
Partial Response (PR): ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease
Stable disease (SD): less than PR.
Progressive disease (PD): sum of the product of dimensions (SPD) of lesions increased ≥50% from smallest value The outcome will be reported as the number of participants with a CR after 4 and 8 cycles of treatment (4 and 8 months), and if CR is achieved anytime within 2 years ("overall").
Secondary Outcome Measures
Magrolimab related Adverse Events
Magrolimab safety and tolerability will be assessed on the basis of magrolimab related adverse events occurring within 4 cycles of treatment (4 months). The outcome will be reported as the number of magrolimab related adverse events judged mild (Grade 1), moderate (Grade 2), severe (Grade 3), life threatening (Grade 4), or fatal (Grade 5), numbers without dispersion.
Full Information
NCT ID
NCT04788043
First Posted
March 4, 2021
Last Updated
March 10, 2023
Sponsor
Stanford University
Collaborators
Merck Sharp & Dohme LLC
1. Study Identification
Unique Protocol Identification Number
NCT04788043
Brief Title
Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma
Official Title
A Phase 2 Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 21, 2022 (Actual)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2027 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Stanford University
Collaborators
Merck Sharp & Dohme LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to test the safety and efficacy of magrolimab in combination with pembrolizumab in patients with Hodgkin lymphoma.
Detailed Description
Primary Objectives:
- To assess the complete remission (CR) rate of magrolimab in combination with pembrolizumab in adult subjects with relapsed or refractory cHL
Secondary Objectives:
To assess the safety and tolerability of magrolimab in combination with pembrolizumab in adult subjects with relapsed or refractory cHL
To assess the overall response rate (ORR)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hodgkin Lymphoma, Classic Hodgkin Lymphoma, Relapsed Classical Hodgkin Lymphoma, Refractory Classic Hodgkin Lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Magrolimab (Hu5F9 G4) and pembrolizumab
Arm Type
Experimental
Arm Description
All subjects will have a baseline PET CT and excisional or core needle biopsy within 1 month of study enrollment and baseline electrocardiogram and laboratory studies within 1 week of study enrollment. All subjects will receive treatment with magrolimab and pembrolizumab according to the dosing schedule. Magrolimab IV given on cycle 1, 2 and 3. Pembrolizumab 200 mg IV given on Cycle 1, 2 and 3. Patients may continue to receive treatment on the study for a maximum of 24 months or until progression of disease, unacceptable toxicity, or bridge to stem cell transplantation (SCT).
Intervention Type
Drug
Intervention Name(s)
Magrolimab
Other Intervention Name(s)
Hu5F9-G4, ONO-7913, anti-CD47 monoclonal antibody Hu5F9-G4
Intervention Description
200 mg max, starting 1 mg/kg IV Infusion
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda, MK-3475, SCH 900475, anti-PD-1 monoclonal antibody MK-3475
Intervention Description
200 mg IV infusion
Intervention Type
Procedure
Intervention Name(s)
PET/CT
Other Intervention Name(s)
Positron Emission Tomography - Computed Tomography (PET/CT)
Intervention Description
Scan
Primary Outcome Measure Information:
Title
Complete Response (CR)
Description
Each participant's response to treatment will be assessed per the Lugano criteria. The criteria are:
Complete Response (CR): Complete disappearance of all lesions, evidence, and effects of disease
Partial Response (PR): ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease
Stable disease (SD): less than PR.
Progressive disease (PD): sum of the product of dimensions (SPD) of lesions increased ≥50% from smallest value The outcome will be reported as the number of participants with a CR after 4 and 8 cycles of treatment (4 and 8 months), and if CR is achieved anytime within 2 years ("overall").
Time Frame
2 years
Secondary Outcome Measure Information:
Title
Magrolimab related Adverse Events
Description
Magrolimab safety and tolerability will be assessed on the basis of magrolimab related adverse events occurring within 4 cycles of treatment (4 months). The outcome will be reported as the number of magrolimab related adverse events judged mild (Grade 1), moderate (Grade 2), severe (Grade 3), life threatening (Grade 4), or fatal (Grade 5), numbers without dispersion.
Time Frame
4 months
Other Pre-specified Outcome Measures:
Title
Overall Response (OR)
Description
Overall response (OR) is defined as the sum of participants who achieve a complete response (CR) plus the number of participants who achieve a partial response (PR). Treatment response will be assessed per the Lugano criteria (aka the Cheson criteria). The criteria are:
CR: Complete disappearance of all lesions, evidence, and effects of disease
PR: ≥50% decrease in SPD of the 6 largest lesions with no increase in the size of the other nodes; splenic / hepatic nodules regress ≥50%, and with no new sites of disease
Stable disease (SD): less than PR.
Progressive disease (PD): sum of the product of dimensions (SPD) of lesions increased ≥50% from smallest value The outcome will be reported as the number of participants with either a CR or a PR after 4 and 8 cycles of treatment (4 and 8 months). For participants who undergo a subsequent stem cell transplant, the value will be recorded as the time to transplant (censored).
Time Frame
8 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Age ≥ 18 years
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1
Biopsy proven relapsed or refractory cHL
Prior treatment with at least two systemic therapies
Metabolically active measurable disease by PET imaging per the 2014 Lugano criteria
Hemoglobin ≥ 9.5 g/dL
Absolute neutrophil count ≥ 1,000 cells/μL without G-CSF support within 3 weeks prior to enrollment
Platelet count ≥ 75,000 cells/μL
Creatinine clearance > 40 mL/min per the Cockroft-Gault formula
Total bilirubin < 1.5 x upper limit of normal (ULN) (or < 3.0 x ULN and primarily unconjugated in subjects with a history of Gilbert's syndrome)
Negative urine or serum pregnancy test within 30 days of enrollment and within 72 hours before the first administration of magrolimab for women of childbearing potential
Women of childbearing potential must be willing to use at least 1 highly effective method of contraception during the study and continue for 4 months after the last dose of magrolimab
Male subjects who are sexually active with a woman of childbearing potential and who have not had vasectomies must be willing to use a barrier method of contraception during the study and for 4 months after the last dose of magrolimab
Ability to understand and the willingness to sign the written IRB approved informed consent document
Must be willing and able to comply with the clinic visits and procedures outlined in the study protocol
Exclusion Criteria:
Prior treatment with a PD-1 inhibitor within 6 months prior to enrollment
Prior treatment with antibodies targeting CD47 or SIRPα2
Prior allogeneic hematopoietic cell transplantation
Systemic autoimmune disorder on chronic immunosuppression (defined as ≥ 10 mg of prednisone daily)
RBC transfusion dependence, defined as requiring more than 2 units of RBCs during the 4-week period prior to screening
History of hemolytic anemia, autoimmune thrombocytopenia, or Evan's syndrome within the last 3 months
Second malignancy not in complete remission for at least 1 year, excluding fully resected non melanoma skin cancer or localized prostate cancer
Women who are pregnant or breast feeding
HIV or hepatitis B or C infection with active viral replication by PCR
Second malignancy not in complete remission for at least 1 year, excluding fully resected non-melanoma skin cancer or localized prostate cancer
Active cardiac disease including unstable angina, decompensated congestive heart failure, or severe uncontrolled conduction abnormalities
History of non-infectious pneumonitis requiring corticosteroids or current pneumonitis
Significant medical conditions, as assessed by the investigators and IND holder, that would substantially increase the risk benefit ratio of participating in the study
History of psychiatric illness or substance abuse likely to interfere with ability to comply with protocol requirements
Received a live or live attenuated vaccine within 30 days before the first dose of study intervention
Received any anti-cancer therapy within 2 weeks prior to the first dose of study intervention
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mariel Rojas
Phone
650-723-0530
Email
mlrojas@stanford.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ranjana H Advani, MD
Organizational Affiliation
Stanford Universiy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94304
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mariel Rojas
First Name & Middle Initial & Last Name & Degree
Ranjana H Advani, MD
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jilian Foreman
Phone
617-582-8713
Email
JillianM_Foreman@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Reid Merryman, MD
First Name & Middle Initial & Last Name & Degree
Margaret Shipp, MD
First Name & Middle Initial & Last Name & Degree
Philippe Armand, MD, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study of Magrolimab and Pembrolizumab in Relapsed or Refractory Classic Hodgkin Lymphoma
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